10 Biopharma Stories to Look Forward to in 2021

 If 2020 taught us anything, it was that unexpected things happen. That said, there are some stories we’ll be watching for. Here’s a look.

1. The end of the pandemic. In 2020, it’s safe to say that the pandemic was far worse than expected—although maybe not as bad as it could have been—and very difficult to predict. Now that in the U.S. and Europe there are two vaccines, with other vaccines, such as Sinovac’s and Russia’s Sputnik V, being deployed in other parts of the world, the expectations are that in 2021 the COVID-19 pandemic will come under control and potentially basically disappear—although most experts seem to believe “under control” is a more likely outcome in the shorter term.

Scott Gottlieb, former director of the U.S. Food and Drug Administration (FDA), noted in December 2020 that he expected the pandemic could “effectively” be ended in 2021 with the launch of the Pfizer-BioNTech and Moderna vaccines. He and others have suggested it will largely be under control by summer, although there are likely to be flare-ups in the Fall.

2. AstraZeneca and University of Oxford COVID-19 vaccine authorization. Early on in the race for a vaccine against COVID-19, AstraZeneca and the University of Oxford’s efforts were leading the way with expectations of being the first to be authorized. In September 2020, the trials were halted to investigate a potentially severe side effect in a UK patient, transverse myelitis, an inflammation of part of the spinal cord. After a short break, the trial restarted in the UK and other parts of the world, but was delayed for much longer in the U.S.

Then in early December, AstraZeneca and the University of Oxford published interim data analysis of their four Phase III trials of their vaccine, with some confounding results. They reported overall efficacy of 70.4%, which was quite a bit lower than that seen with the Pfizer-BioNTech and Moderna vaccines, which were both around 95%. But further confusing the issue was that about 1800 participants accidentally received a first dose that was only about half the intended dose. But in those participants, the efficacy was about 90%, while in the broader dosing regimen it was 62%. The reason for this is still not understood and many regulators may want it to be explained before authorizing it for broader use.

As of December 27, 2020, the UK government was reviewing vaccines from both AstraZeneca and Moderna. Approximately 40% of the AstraZeneca-Oxford vaccine has been reserved for low- and middle-income countries.

3. Johnson & Johnson’s COVID-19 vaccine. On December 17, 2020, Johnson & Johnson, which is running probably fourth for U.S. and European COVID-19 vaccine development, announced their Phase III ENSEMBLE trial was fully enrolled with about 45,000 participants. They hope to have interim data from the trial available by the end of January 2021, and if it is safe and effective, plans to submit for Emergency Use Authorization (EUA) to the FDA in February, with other global health regulators following immediately afterwards. One of the reasons this is promising is that unlike the other three vaccines mentioned above, the J&J vaccine only needs a single dose—at least that’s the theory so far. If everything goes well, then there would be a single-dose vaccine that could be widely deployed, which would require less manufacturing and more manageable storage than the others. The Pfizer-BioNTech vaccine requires extremely cold storage temperatures, with the Moderna requiring more typical freezing temperatures found in standard refrigerators.
    
4. Biogen’s aducanumab. One way or the other, Biogen’s aducanumab for Alzheimer’s disease is likely to be a big story in 2021. In March 2019, Biogen and its collaboration partner, Tokyo-based Eisai, announced they were discontinuing the ENGAGE and EMERGE Phase III trials of the drug in patients with mild Alzheimer’s because it wasn’t likely to hit the primary endpoints. Then, in July, after analyzing completed data and with talks with the FDA, they decided they were going to pursue regulatory approval for the drug. In early December 2019, they presented full data at the 12th Clinical Trials on Alzheimer’s Disease (CATD) conference. The company argued that the Phase III EMERGE trial met its primary endpoint, demonstrating a significant decrease in clinical decline in a subset of patients that received a high enough dose of the drug.

In November 2020, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted 1 yes, 8 no, and 2 uncertain on the question of whether the EMERGE trial provided evidence that supported the effectiveness of aducanumab. Other similar questions also had similar votes. In short, the advisory committee did not vote to recommend the drug to the agency, which has a PDUFA date of March 7, 2021 to decide whether to approve the aducanumab Biologics License Application (BLA).

5. Biden Administration and drug pricing. At this point, incoming President Joe Biden has announced plans to lower drug prices building on the foundations of the Affordable Care Act. Some his plans include repealing the rules that prevent drug companies from directly negotiating with Medicare over drug prices. And he wants to limit the launch prices of new drugs that have no competition and “are being abusively priced by manufacturers.” The Biden plan also calls for Health and Human Services to establish an independent review board to assess the value of a new drug. The board will then recommend a “reasonable price” based on the average price in other countries or, if the drug is entering the U.S. market first, based on an evaluation by the independent board members.

Another Biden plan opens up foreign markets for consumers to buy their prescription drugs and calls for limiting price increases on branded drugs and generics for drugs included in the Medicare program. It also calls for ending the tax deductions that pharmaceutical companies can take for the amount of money it spends on advertising its medications.

6. M&A. Mergers and acquisitions (M&A) were not a huge factor in 2020, although there was quite a bit more venture capital funding than was initially expected, somewhat driven by an increased focus on biotech and pharma with the ongoing COVID-19 pandemic. Four big companies are cited as possible tasty takeover targets for 2021. They are:

• BioMarin Pharmaceutical. The company has a market cap of $15.4 billion and focuses on rare diseases, with six commercially approved drugs.

• uniQure. UniQure has a market cap of $2.1 billion. It is a strong potential player in the gene therapy space. Its lead candidate is AMT-061, an AAV5-based gene therapy being evaluated for severe and moderately severe hemophilia B in the Phase III HOPE-B study.

• Regenxbio. With a market cap of $1.6 billion, Regenxbio is also a gene therapy company. Its most advanced compound is RGX-314, in a Phase I/IIa trial for wet age-related macular degeneration. It also is developing three other gene therapies for rare neurological diseases.

• Deciphera Pharmaceuticals. Deciphera has a market cap of $3.2 billion. Its Qinlock was approved for advanced gastrointestinal stromal tumor (GIST) in May 2020 by the FDA. It is also being developed for GIST in other treatment settings and has several pipeline compounds for oncology.

7. Venture Capital. PitchBook projected that venture capital (VC) activity for 2021 will exceed $20 billion. They think this is being fueled by growing capital commitments from VC investors hoping to enter the biopharma space, as well as recycling of profits and liquidity from this year’s initial public offering (IPO) market. So expect a lot of biotech startups and newer biotech companies to announce funding rounds.

“As we head into the new year, there are many variables on the table including the COVID-19 pandemic, a new administration in the U.S. with numerous policy proposals spanning taxes, immigration, trade and an array of other issues that directly affect both VC investors and companies,” said James Gelfer, senior strategist at PitchBook. “While macro uncertainty remains high, a light is beginning to appear at the end of the tunnel, and we see continued opportunity for innovation as investors, companies and regulators have seemingly embraced the new landscape and committed to increasing access to capital.”

One of the reasons they expect VC spending in biopharma to expand is that during 2020, particularly from March through about July, many pharma companies, if able, paused their clinical trials. Now that the vaccines are rolling out and expectations are that the pandemic will be brought under control by mid-2021 or earlier, more normal drug development activity will continue.

8. BioMarin Pharmaceutical’s Roctavian for hemophilia B. In August 2020, the FDA issued a Complete Response Letter (CRL) for BioMarin’s Roctavian (valoctocognee roxaparvovec) for severe hemophilia A. The FDA recommended another two years of data from its ongoing 270-301 Phase III study to evaluate the durable effect using Annualized Bleeding Rate (ABR) as the primary endpoint. On the surface, that would suggest that the earliest the company could turn things around and get the drug onto market was in 2021.

But, the trial will have one-year results for all 134 participants early in 2021. Some of those 134 participants would have been followed for 18 to 24 months at that time, would if the data is supportive, could lead to an earlier turnaround for a resubmission.

9. Bluebird bio’s ide-cel for relapsed and refractory multiple myeloma. In July 2020, Bristol Myers Squibb and bluebird bio resubmitted the BLA for idecabtagene vicleucel (ide-cel) for adults with relapsed and refractory multiple myeloma (RRMM). The resubmission included more details on the Chemistry, Manufacturing and Controls (CMC) module the FDA wanted after the original BLA submission in March 2020. The therapy was granted Breakthrough Therapy Designation by the FDA and Priority Medicines (PRIME) designation by the European Medicines Agency. Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy. The PDUFA date is March 27, 2021. If approved, it would be bluebird’s first commercial-stage drug.

10. TG Therapeutics’ umbralisib for marginal zone lymphoma and follicular lymphoma. The FDA accepted TG Therapeutics’ New Drug Application (NDA) for umbralisib on August 13, 2020, with a PDUFA date of February 15, 2021for MZL and for FL in June 15, 2021. Umbralisib is a once-daily, oral, dual inhibitor of PI3K-delta and CK1-epsilon.

The MZL indication was accepted under Breakthrough Therapy Designation and Priority Review. The submissions were mostly based on data from the umbralisib monotherapy MZL and FL cohorts of the UNITY-NHL Phase IIb trial evaluating patients with r/r MZL or FL. Each cohort had met its primary endpoint of overall response rate (ORR), hitting the company’s target guidance of 40-50% ORR. If approved, either would be the first for the company.

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